Health Inc Research Articles

Design, Recruitment, and Baseline Characteristics of a Virtual 1-Year Mental Health Study on Behavioral Data and Health Outcomes: Observational Study.

BackgroundDepression and anxiety greatly impact daily behaviors, such as sleep and activity levels. With the increasing use of activity tracking wearables among the general population, there has been a growing interest in how data collected from these devices can be used to further understand the severity and progression of mental health conditions.ObjectiveThis virtual 1-year observational study was designed with the objective of creating a longitudinal data set combining self-reported health outcomes, health care utilization, and quality of life data with activity tracker and app-based behavioral data for individuals with depression and anxiety. We provide an overview of the study design, report on baseline health and behavioral characteristics of the study population, and provide initial insights into how behavioral characteristics differ between groups of individuals with varying levels of disease severity.MethodsIndividuals who were existing members of an online health community (Achievement, Evidation Health Inc) and were 18 years or older who had self-reported a diagnosis of depression or anxiety were eligible to enroll in this virtual 1-year study. Participants agreed to connect wearable activity trackers that captured data related to physical activity and sleep behavior. Mental health outcomes such as the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder Questionnaire (GAD-7), mental health hospitalizations, and medication use were captured with surveys completed at baseline and months 3, 6, 9, and 12. In this analysis, we report on baseline characteristics of the sample, including mental health disease severity and health care utilization. Additionally, we explore the relationship between passively collected behavioral data and baseline mental health status and health care utilization.ResultsOf the 1304 participants enrolled in the study, 1277 individuals completed the baseline survey and 1068 individuals had sufficient activity tracker data. Mean age was 33 (SD 9) years, and the majority of the study population was female (77.2%, 994/1288) and identified as Caucasian (88.3%, 1137/1288). At baseline, 94.8% (1211/1277) of study participants reported experiencing depression or anxiety symptoms in the last year. This baseline analysis found that some passively tracked behavioral traits are associated with more severe forms of anxiety or depression. Individuals with depressive symptoms were less active than those with minimal depressive symptoms. Severe forms of depression were also significantly associated with inconsistent sleep patterns and more disordered sleep.ConclusionsThese initial findings suggest that longitudinal behavioral and health outcomes data may be useful for developing digital measures of health for mental health symptom severity and progression.

Leaving No Large Vessel Occlusion Stroke Behind: Reorganizing Stroke Systems of Care to Improve Timely Access to Endovascular Therapy.

Leaving No Large Vessel Occlusion Stroke Behind: Reorganizing Stroke Systems of Care to Improve Timely Access to Endovascular Therapy.

Prognostic implications of gene amplifications identified by circulating tumor DNA (ctDNA) analysis in metastatic prostate cancer (mPC).

e17594 Background: mPC is a dynamic disease that confers a poor prognosis- particularly in the metastatic castration-resistant prostate cancer (mCRPC) setting. Analysis of ctDNA provides an opportunity to identify and monitor somatic alterations (SAs) in a patient’s treatment course. However, how certain SAs can inform disease management is not fully characterized. We evaluated whether the presence of specific gene amplifications (GAs) and changes in plasma copy number (PCN) are associated with disease features and prognosis. Methods: This is a retrospective study of mPC patients seen at the Hollings Cancer Center between 2015-2019 who underwent ctDNA profiling using Guardant360 (Guardant Health Inc). Guardant360 identifies SAs and GAs of select genes by NGS. Descriptive statistics were used to summarize baseline patient characteristics. The chi-square test and odds ratio (OR) were used to evaluate associations between clinical factors and GAs. The Kaplan-Meier method was used to estimate OS from either the date of GA detection or the initiation of systemic therapy. Results: 130 men with mPC were identified as having ≥1 GA. The presence of liver and/or lung metastases were associated with GAs of BRAF (OR 2.5; 95%CI 1.1-5.8, p < 0.05) , CDK6 (OR 2.3; 95%CI 1.4-8.0, p < 0.01) , PI3KCA (OR 4.4; 95%CI 1.8-10.7, p < 0.01) , and FGFR1 (OR 3.1; 95%CI 1.1-9.0, p = 0.038). These GAs were also associated with having ≥2 concurrent GAs (p < 0.01 for each gene). From this cohort, survival analyses were completed on 59 patients with mCRPC. Men with only 1 GA, compared to men with ≥2 GAs, had improved median survival (mo.) from date of initial GA(s) detection (16.5 vs 9.4, p < 0.01) or therapy initiation (16.0 vs 9.0, p < 0.01). Among men with mCRPC, AR and/or MYC GA, median survival improved in men who had reduction in AR or MYC PCN during therapy compared to men without a PCN decrease (25.1 vs 15.9 p < 0.01). Conclusions: Patients with mPC who had liver and/or lung metastases were associated with having specific GAs in BRAF, CDK6, PI3KCA, and FGFR1. Notably, the presence of liver or lung metastases was not associated with AR GA. In mCRPC, patients with ≥2 GAs had decreased OS compared to men with one GA. Having an increased number of GAs is likely reflective of greater chromosomal instability and be associated with more aggressive disease. Our study reveals serial monitoring of AR and MYC PCN during therapy demonstrated reduced OS in patients without PCN reduction. This supports the use of serial ctDNA monitoring of PCN to inform therapeutic response and prognosis.

AUA ANNUAL MEETING PROGRAM ABSTRACTS 2020: ACCREDITATION, DISCLAIMER AND COPYRIGHT

You have accessJournal of UrologyAUA ANNUAL MEETING PROGRAM ABSTRACTS 20201 Apr 2020AUA ANNUAL MEETING PROGRAM ABSTRACTS 2020: ACCREDITATION, DISCLAIMER AND COPYRIGHT View All Author Informationhttps://doi.org/10.1097/01.JU.0000661540.21831.e9AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail ACCREDITATION STATEMENT: The American Urological Association Education and Research, Inc. is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The American Urological Association Education and Research, Inc. takes responsibility for the content, quality and scientific integrity of the CME Activity. DISCLAIMER The statements and opinions contained in the articles of The Journal of Urology® are solely those of the individual authors and contributors and not of the American Urological Association Education and Research, Inc. (AUAER). The content of this publication may contain discussion of off-label uses of some of the agents mentioned. Please consult the prescribing information for full disclosure of approved uses. To the extent permissible under applicable laws, no responsibility is assumed by the AUAER for any injury and/ or damage to persons or property as a result of any actual or alleged libelous statements, infringement of intellectual property or privacy rights, or products liability, whether resulting from negligence or otherwise, or from any use of operation of any ideas, instructions, procedures, products or methods contained in the material therein. The abstracts are being reprinted without editorial review. COPYRIGHT AND PERMISSIONS:The Journal of Urology® including supplements is the Official Journal of the American Urological Association Education and Research, Inc. and is published monthly by Wolters Kluwer Health Inc. The American Urological Association grants the Publisher full and exclusive publishing and distribution rights, worldwide, for both print and electronic media. Therefore no portions of the work(s) can be reproduced without written consent from the Publisher. Permissions and photocopying: For permission and/ or rights to use content for which the copyright holder is Wolters Kluwer or the society we have partnered with the Copyright Clearance Center to provide permissions for our products through their RightsLink service, please go to the journal's website and after clicking on the relevant article, click on the Get Content & Permissions link under the Article Tools box that appears on the right side of the page. For questions about the Rightslink service, e-mail [email protected]com or call 877-622-5543 (U.S. Only) or 978-777-9929. Permissions FAQs and information on authors permission requests are available at https://shop.lww.com/journal-permission. For additional permission inquiries, please contact [email protected]com. Copyright © 2020 by the American Urological Association Education and Research, Inc. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Expand All Advertisement Advertisement PDF downloadLoading ...

Abstract OT2-02-03: NSABP FB-13: An assessment of the biological and clinical effects of palbociclib with ovarian suppression and letrozole in the neoadjuvant treatment of pts (pts) with premenopausal (preM) estrogen-receptor positive/HER2-negative primary breast cancer

Abstract Background: There have been few studies of neoadjuvant endocrine therapy in premenopausal (preM) women despite low pathologic complete response (pCR) rates using neoadjuvant chemotherapy in ER+/HER2− pts. Suppression of Ki67, particularly complete cell cycle arrest (CCCA) defined as Ki67 <2.7% after 2 wks of neoadjuvant endocrine therapy has been demonstrated to correlate with recurrence-free survival. PALLET, a randomized, neoadjuvant endocrine trial evaluated letrozole (AI) v palbociclib (pal) in combination with AI for 14 wks in post-menopausal women. This study demonstrated a modest improvement in clinical response (54.3% with the combination v 49.5% with AI alone) but showed a significant difference in achievement of CCCA (Ki67<2.7%) with the combination of pal and AI v AI alone (90% v 59%). We seek to evaluate this combination, given over a longer duration in the neoadjuvant setting, in preM women with early-stage breast cancer. Trial design: FB-13 is a phase II, open-label study to examine the biological and clinical effect of neoadjuvant endocrine therapy with AI, pal, and ovarian suppression in preM pts with ER+, HER2-negative early invasive breast cancer. 76 pts will be stratified into one of two approximately equal sized cohorts based on Oncotype DX Breast Recurrence Score (RS) (cohort 1: pts with RS <11 or cohort 2: pts with RS 11 to <26). A baseline tumor biopsy prior to start of therapy (tx) for RS and Ki67 will both be centrally determined. Pts in both cohorts will receive letrozole 2.5 mg by mouth daily, pal 125 mg by mouth daily for 21 days of a 28-day cycle, and goserelin 3.6 mg SQ injection every 28 days. At wk 6, pts will have core-cut biopsies for real-time evaluation of Ki67. Pts from both cohorts who have Ki67 <10% will continue tx for a total of 6 cycles. Pts with a persistent Ki67 ≥10% will permanently discontinue tx and begin neoadjuvant chemotherapy or proceed to surgery at physician discretion. Eligibility: FB-13 is enrolling preM women newly diagnosed with ER+/HER2− early breast cancer who are candidates for neoadjuvant endocrine therapy. Pts must be preM based on standard definitions. Primary tumor size must be >2 cm. RS must be <26. Mandatory pre-treatment and post-surgical samples will be collected and analyzed for RS and Ki67, as well as additional biomarkers to correlate with response. Blood will be collected at baseline, 4 wks, and at 24 wks for estradiol levels to demonstrate ovarian suppression. A 4-wk estradiol level in the postmenopausal range will be required to receive further treatment. Specific aims: The primary aim is to determine complete cell cycle arrest as indicated by a Ki67 <2.7% at 6 wks. Secondary aims are to determine overall response rate (ORR) by clinical exam and ultrasound, the pCR, to generate a Preoperative Endocrine Prognostic Index (PEPI score), to compare the change in Ki67 at baseline, after 6 wks and 24 wks, and to determine the rate of breast-conservation therapy. Statistical methods: We anticipate that the addition of palbociclib to ovarian suppression and AI will result in a measurable drop in Ki67 and a high ORR. The null hypothesis is ORR <40% and alternative hypothesis is ORR >60%. We anticipate that >60% of pts in each cohort will have 6 wk Ki67 <2.7% and clinical response >35%. Present accrual and target accrual: Currently 12 of a planned 76 pts have been enrolled. NSABP Operations contact information: Diana Gosik, Diana.Gosik@nsabp.org NCT03628066 SUPPORT: Genomic Health Inc, Pfizer, NSABP Foundation Citation Format: Shannon Puhalla, Greg Yothers, Amy P Sing, Thomas B Julian, Norman Wolmark, Samuel A Jacobs. NSABP FB-13: An assessment of the biological and clinical effects of palbociclib with ovarian suppression and letrozole in the neoadjuvant treatment of pts (pts) with premenopausal (preM) estrogen-receptor positive/HER2-negative primary breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-02-03.

499P - Prevalence of uncommon epidermal growth factor receptor (EGFR) alterations detected by circulating tumour DNA (ctDNA) in non-small cell lung cancer (NSCLC) patients in Hong Kong

BackgroundEGFR mutations occur in about half of the advanced non-squamous NSCLC patients in East Asia. Majority of the common activating mutations like L858R, exon 19 deletions (del) and T790M are detected by hot spot test methods in Hong Kong. However, hot spot test may not detect other uncommon EGFR alterations like point mutations, exon 20 insertions and amplifications, in which the best treatment remains undefined. Using a comprehensive liquid biopsy we investigated the prevalence of these uncommon EGFR alterations in ctDNA from NSCLC patients. MethodsAll Guardant360 (Guardant Health, Redwood City, CA) requests ordered in Hong Kong between Jan 2016 and June 2019 were reviewed. This is a next-generation ctDNA sequencing (NGS) panel of 74 cancer-related genes, including complete exon sequencing of EGFR. We identified cases with a diagnosis of “lung cancer” and excluded pure squamous, small cell, neuroendocrine and sarcomatoid histology. Uncommon EGFR alterations, defined as amplification or mutations other than L858R, exon 19 del, or T790M were identified. Synonymous mutations and variants of unknown significance were excluded. Demographics and impact of results to subsequent management will be analyzed and presented later. ResultsA total of 282 non-squamous NSCLC patients were tested. Samples came from 146 women and 136 men, with a median age 60. ctDNA was identified in 241 samples (85.5% detection rate). EGFR alterations were identified in 95 samples (39.4%), including L858R (48), exon 19 del (27), and T790M (24). Uncommon alterations were found in 47 of 95 EGFR cases (49.5%); 18 of these had no co-existing common EGFR or other driver mutation. These included amplifications (8); exon 20 insertions (8); L861Q (2); and other point mutations (4); 4 cases had an uncommon mutation with amplification. ConclusionsUsing a comprehensive ctDNA NGS panel, 47 out of 241 (19.5%) non-squamous NSCLC patients with uncommon EGFR alterations were detected. Novel NGS methods can help identify this group of patients with unmet needs for a gene-directed therapy. Legal entity responsible for the studyGuardant Health AMEA. FundingHas not received any funding. DisclosureO.S.H. Chan: Full / Part-time employment: Hong Kong Integrated Oncology Centre; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Merck Sharp & Dohme. G.Y. Cheung: Full / Part-time employment: Sanomics Limited. M.M.L. Lee: Full / Part-time employment: Guardant Health AMEA. S. Olsen: Full / Part-time employment: Guardant Health AMEA; Shareholder / Stockholder / Stock options: Guardant Health Inc; Shareholder / Stockholder / Stock options: AstraZeneca.

1877PD - Prevalence and prognostic effect of high tumor mutation burden (TMB-H) across multiple less common solid cancers using a real-world dataset

BackgroundLittle is known about the prognostic effect of TMB-H among patients with less common cancers who did not receive an immunotherapy (IO). MethodsThe de-identified Flatiron Health-Foundation Medicine (FMI) Clinico-Genomic Database was used to select patients (pts) with any of 10 solid cancers (Table). 109 Pts with confirmed microsatellite instability-high (MSIH) cancers were excluded, of which 101 pts were endometrial cancer. TMB-H was defined as≥10 mutations per megabase (Mut/Mb) with an additional analysis using a cutoff of 13 Mut/Mb. For overall survival (OS) analysis, Pts with IO were excluded if start of IO earlier than or equal to FMI report date (69 pts), or censored if start of IO later than FMI report date (243 pts). OS was analyzed using Kaplan-Meier method and Cox proportional hazard model, adjusting for age, gender, cancer types, practice type and albumin. A non-inferiority test of TMB-H having longer OS than TMB-low (-L) was carried out with a prespecified hazard ratio (HR) of 0.75. ResultsOf the 2,589 pts (table), average age at diagnosis was 64 years and 65% were female. Median TMB was 2.6 Mut/Mb overall, ranged from 1.7 (Meso, salivary, thyroid) to 8.7 (SCLC) Mut/Mb. Overall 12.8% were TMB-H with the highest in SCLC (40.0%) and lowest in meso (1.2%). The adjusted HR (AHR) of TMB-H vs. -L was 0.94 (95% CI: 0.77-1.13) for OS from FMI report date, which met the prespecified threshold for non-inferiority by rejecting the null hypothesis. The AHR was 0.84 (0.67-1.05) using alternative cutoff of 13 Mut/Mb. Comparable results were observed when including MSI-H pts and calculating OS from 1st observed antineoplastic treatment date.Table: 1877PDTable: 1877PDNTMB-HOS (month, 95%CI)HRadjustPadjustn%TMB-HTMB-LTotal2,58933212.88.4 (7.4; 11.4)10.5 (9.5; 11.5)0.94 (0.77; 1.13)0.491SCLC30512240.06.4 (5.4; 7.5)7.4 (5.5; 10.5)1.03 (0.74; 1.44)0.863Neuroendocrine1644829.310.4 (6.4; NA)6.4 (4.5; 10.5)0.83 (0.48; 1.44)0.506Cervical1141714.9NA (6.4; NA)7.4 (4.4; 11.5)0.32 (0.08; 1.31)0.113Anal1251713.67.4 (2.5; NA)7.5 (5.5; 15.4)0.84 (0.40; 1.79)0.659Vulvar30413.38.5 (0.5; NA)6.5 (2.5; NA)1.18 (0.22; 6.29)0.848Salivary1692213.04.5 (3.5; NA)15.5 (10.5; 21.5)1.20 (0.48; 2.99)0.691Endometrial5906611.211.4 (8.5; 26.5)13.5 (11.5; 15.4)1.15 (0.75; 1.75)0.522Biliary706284.011.5 (7.4; NA)8.4 (7.4; 10.4)0.65 (0.35; 1.19)0.162Thyroid22362.710.2 (1.5; NA)27.5 (21.5; NA)1.64 (0.39; 6.96)0.502Meso16321.2NA12.5 (8.5; 15.5)-0.997 ConclusionsThere is a wide range of TMB among these cancers. Non-inferiority testing and HR estimates comparing OS for TMB-H (≥10 Mut/Mb) vs. -L did not support an effect of TMB on OS in the absence of IO for these cancers. Further research is needed to explore whether the prognostic effect of TMB varies by tumor type or threshold. Legal entity responsible for the studyMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. FundingMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. DisclosureD. Backenroth: Shareholder / Stockholder / Stock options, Full / Part-time employment: Flatiron Health Inc. C. Shao: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co. G. Li: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. L. Huang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co.. S.K. Pruitt: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc.. E. Castellanos: Full / Part-time employment: Flatiron Health Inc.. G.M. Frampton: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. K.R. Carson: Full / Part-time employment: Flatiron Health Inc.. T. Snow: Full / Part-time employment: Flatiron Health Inc.. G. Singal: Full / Part-time employment: Foundation Medicine. D. Fabrizio: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. B.M. Alexander: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. F.J. Jin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc.. W. Zhou: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc..

440O - Phase I study of the arginase inhibitor INCB001158 (1158) alone and in combination with pembrolizumab (PEM) in patients (Pts) with advanced/metastatic (adv/met) solid tumours

440O - Phase I study of the arginase inhibitor INCB001158 (1158) alone and in combination with pembrolizumab (PEM) in patients (Pts) with advanced/metastatic (adv/met) solid tumours

Bioavailability of Iron Supplement Formulations by Bariatric Surgery Type: A Pilot Study (P23-013-19)

ObjectivesOur previous research demonstrated that ferrous sulfate, the gold standard iron supplement treats iron deficiency in bariatric surgery patients but wasn’t well tolerated. We also found that the bioavailability of iron supplements, assessed by a serum iron absorption test, predicts treatment response. The objective of the current study is to determine whether bariatric surgery type (gastric bypass [GB] and sleeve gastrectomy [SG]) or iron formulation type (inorganic ferrous sulfate versus and an organic, slow-release form of iron, called AspironTM) predicts iron supplement bioavailability. MethodsIron-deficient GB and SG females, ages 18–65 years, who had surgery at least 6 months previously, participated in an 8-hour iron absorption test. Participants were considered iron deficient if two of the following values were abnormal: serum transferrin receptor greater than 2012 mcg/L, ferritin below 30 mcg/L, total iron binding capacity above 370 mcg/dL, and a serum transferrin receptor: ferritin ratio greater than 500. Participants received a low-iron breakfast with a 65 mg iron supplement. We assessed serum iron every 30 minutes for 8 hours following the supplementation using a calorimetric assay (South Bend Medical Foundation, South Bend, IN). ResultsWe report our preliminary findings to date; the study is ongoing. Out of the 10 participants, 8 had GB and 2 had SG. Six of the GB patients and both SG patients received AspironTM, and two of the GB patients received ferrous sulfate. In GB participants, following ferrous sulfate, serum iron increased 80.5 ± 6.4 mcg/dL compared to baseline, whereas following AspironTM, serum iron increased 6.7 ± 4.6 mcg/dL compared to baseline (P = 0.000). Compared to the GB group, serum iron increased 58.5 ± 57.3 mcg/dL in the SG group following AspironTM supplementation (P = 0.037). ConclusionsOur preliminary findings suggest that AspironTM is not as bioavailable as ferrous sulfate in GB patients. AspironTM may be better absorbed in SG patients, indicating that it could be an effective treatment to reverse iron deficiency in the SG population. Funding SourcesCura Global Health Inc.

Expected Monetary Impact of Oncotype DX Score-Concordant Systemic Breast Cancer Therapy Based on the TAILORx Trial.

TAILORx demonstrated that women with node-negative, hormone receptor-positive, HER2-negative breast cancers and Oncotype DX recurrence scores (RS) of 0-25 had similar 9-year outcomes with endocrine vs chemo-endocrine therapy; evidence for women aged 50 years and younger and RS 16-25 was less clear. We estimated how expected changes in practice following the trial might affect US costs in the initial 12 months of care (initial costs). Data from Surveillance, Epidemiology, and End Results (SEER), SEER-Medicare, and SEER-Genomic Health Inc datasets were used to estimate Oncotype DX testing and chemotherapy rates and mean initial costs pre- and post-TAILORx (in 2018 dollars), assuming all women received Oncotype DX testing and score-suggested therapy posttrial. Sensitivity analyses tested the impact on costs of assumptions about compliance with testing and score-suggested treatment and estimation methods. Pretrial mean initial costs were $2.816 billion. Posttrial, Oncotype DX testing costs were projected to increase from $115 to $231 million and chemotherapy use to decrease from 25% to 17%, resulting in initial care costs of $2.766 billion, or a net savings of $49 million (1.8% decrease). A small net savings was seen under most assumptions. The one exception was if all women aged 50 years and younger with tumors with RS 16-25 elected to receive chemotherapy, initial care costs could increase by $105 million (4% increase). Personalizing breast cancer treatment based on tumor genetic profiles could result in small cost decreases in the initial 12 months of care. Studies are needed to evaluate the long-term costs and nonmonetary benefits of personalized cancer care.

A new hope for early psychosis care: the evolving landscape of digital care tools.

Improving understanding of and outcomes for early-course psychosis (ECP) is a recognised global mental health priority. We argue digital health technologies can advance care for ECP by better accounting for clinical heterogeneity, offering better predictive models, increasing access to early interventions and enhancing existing treatment options.Declaration of interestL.M.T. owns shares in Safari Health Inc - a digital health technology company.

Commonwealth of the Northern Mariana Islands

Commonwealth of the Northern Mariana Islands Zaldy Dandan When the period in review began, one of the two biggest concerns for Commonwealth of the Northern Mariana Islands (CNMI) leaders and policy-makers was the looming end of the federal cw (CNMI-only Transitional Worker) program, which provides special cw-1 visas that allow non-US citizens to work in the CNMI. Set to expire in December 2019, the cw program has provided the bulk of the workers making up the CNMI private sector, providing much-needed support to the economy. The other concern was the November 2018 general election. During the period under review, the party in power, the local Republican Party, could feel the wind in its sails. The local economy, whose spectacular downturn started in 1998, was finally recovering. For the first time in so many years, tourist numbers were up, and there were new investors actually investing in the CNMI (US Government Accountability Office 2017). More economic activities meant more government revenue, and the issues that had bedeviled previous administrations and legislatures—the lack of funding for critical services, agencies, and outstanding obligations, among them the pension fund—could now be addressed. But, as the late veteran newscaster Eric Sevareid is widely attributed to have said, the chief cause of problems are solutions. For some residents, their main concern was no longer the economy but "overdevelopment" (mv, 29 June 2018). For these residents, the gaudy Saipan casino, still under construction, symbolized larger issues in the Commonwealth. Opponents of the Saipan casino argued that voters should have been able to approve its legalization. Proponents, however, argued that the casino legalization went through the proper legal process. The casino bill was signed into law by then-Governor Eloy S Inos, who said that it was the only way to prevent the collapse of the pension fund. Opponents of the new law challenged it in court, saying that its passage violated the Open Government Act's requirement that the legislature issue a meeting notice at least seventy-two hours before the meeting. The CNMI Legislature responded by passing another Saipan casino law that complied with the notice requirement. Since the exclusive us$2 billion casino license was awarded in July 2014 to Best Sunshine International, now known as Imperial Pacific International, opponents have doubted its viability. For their part, the casino owners have seemed to have a knack for attracting or creating controversies. Imperial Pacific management hired contractors from China who turned out to have brought in construction workers on tourist visas—the "quickest" way, given the federal restrictions on the hiring of guest workers (mv, 29 May 2017). This illegal activity unraveled just as quickly following the accidental death of one of the "tourists" at the casino's construction site (mv, 3 April 2017). Imperial Pacific then did what it should have done from the get-go: It employed a US contractor who hired h2-b (employment visa) workers (mv, 16 July 2018). In July 2017, the casino had a "soft [End Page 180] opening" at its still-unfinished hotel in Garapan, where it had relocated from its previous site, an area in nearby T Galleria (mv, 7 July 2017). Meanwhile, the remaining Chinese "tourists" hired by Imperial Pacific's contractors staged protests near the new casino, demanding back wages and additional compensation (mv, 13 Dec 2017). On Guam, the island's legislative committee on ethics announced that it was launching a full investigation into a complaint against Guam Senator James Espaldon for facilitating a questionable us$11.5 million generator deal, which the CNMI's Commonwealth Utilities Corporation (cuc) ultimately had to scrap (gdp, 17 May 2017). The controversy over this project also resulted in CNMI Governor Ralph Deleon Guerrero (D L G) Torres's decision to "ask" cuc board members to resign (mv, 15 May 2017). In the health sector, Esther Muna, chief executive officer of the Commonwealth Healthcare Corporation (chcc), expressed her desire to evict Pacific Health Inc (phi), the privately owned pharmacy doing business in the CNMI's only hospital, the Commonwealth Health Center, if phi would not agree to a rent increase. But Muna said the governor "disagreed" with the higher amount that chcc...

Clinical Testing of Hemechip in Nigeria for Point-of-Care Screening of Sickle Cell Disease

In sub-Saharan Africa, nearly a quarter of a million babies are born with sickle cell disease (SCD) each year. An estimated 50-90% of these babies die before age 5 due to lack of early diagnosis and timely treatment. The World Health Organization estimates that more than 70% of SCD related deaths are preventable with simple, cost-effective interventions, such as early screening followed by affordable and widely available treatment regimens. Here, we present the early clinical testing results of HemeChip, which is the first single-use cartridge-based microchip electrophoresis hemoglobin screening platform. HemeChip was developed by Hemex Health, Inc., based on technology licensed from Case Western Reserve University. HemeChip allows affordable, objective, quantitative screening of hemoglobin variants at the point-of-care. HemeChip works with a drop of finger or heel-prick blood and separates hemoglobin variants on a piece of cellulose acetate paper that is housed in an injection molded plastic cartridge with a precisely controlled electric field.HemeChip works with a portable reader to produce easily understandable, objective, and quantitative descriptions of the hemoglobin types and percentages present in a blood sample. The HemeChip reader guides the user step-by-step through the test procedure with animated on-screen instructions to minimize user errors. Hemoglobin identification and quantification is automatically done with a custom software on the reader. HemeChip reader records and analyzes the hemoglobin electrophoresis real-time, and it can wirelessly transmit the test results to a central electronic database, if needed.HemeChip prototype units have been clinically tested and benchmarked against the clinical standard technique in Kano, Nigeria, where the SCD prevalence is the highest in the world. We tested a total of 248 subjects (228 children aged 6 weeks to 5 years in Kano, Nigeria; and 20 adults in Cleveland, Ohio, United States) under institutional review board approval, using both HemeChip and the clinical standard laboratory method, High Performance Liquid Chromatography (HPLC, VARIANT™ II, Bio-Rad Laboratories, Inc., Hercules, California). HemeChip tests were done on eHealth Africa campus in Kano, Nigeria, by trained local healthcare workers using blood samples collected at the nearby Aminu Kano Teaching Hospital. Clinical standard (HPLC) testing was done independently by the International Foundation Against Infectious Disease in Nigeria (IFAIN, Abuja, Nigeria) for the blood samples obtained in Kano or by the University Hospitals Cleveland Medical Center Clinical Laboratories (Cleveland, Ohio) for the blood samples obtained in Cleveland.Test results included the following: homozygous SCD (HbSS), heterozygous sickle hemoglobin C disease (HbSC), heterozygous sickle trait (HbAS), and normal (HbAA). HemeChip identified the subjects with HbSS with 100% accuracy, HbSC with 100% accuracy, HbAS with 98.2% accuracy, and HbAA with 96.4% accuracy in comparison to HPLC (Table 1). Overall accuracy of HemeChip was 97.2% in comparison to HPLC for the subjects tested. HemeChip sensitivity was 100% for all hemoglobin variants tested (Table 2), and specificity was 96.4% for HbSS vs. HbAA, 98.2% for HbSS vs. HbAS, 100% for HbSC vs. HbAS, and 100% for HbAS vs. HbAA. Bland-Altman analysis indicated strong agreement between the quantitative HPLC and HemeChip results for hemoglobin percentages, with a mean bias of -3.2%.HemeChip enables, for the first time, accurate, cost-effective identification and quantification of hemoglobin variants at the point-of-need. HemeChip has been developed based on a versatile, mass-producible microchip electrophoresis platform technology that may address other unmet needs in biology and medicine that require rapid, decentralized hemoglobin or protein analysis, identification, and/or quantification. [Display omitted] DisclosuresThota:Hemex Health Inc: Employment. Little:PCORI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria; NHLBI: Research Funding; Doris Duke Charitable Foundations: Research Funding.

Software-guided insulin dosing improves intrapartum glycemic management in women with diabetes mellitus

During labor, maintenance of maternal euglycemia is critical to decrease the risk of neonatal hypoglycemia and associated morbidities. When continuous intravenous insulin infusion is needed, standardized insulin dosing charts have been used for titration of insulin to maintain glucose in target range. The GlucoStabilizer software program (Indiana University Health Inc, Indianapolis, IN) is a software-guided insulin dosing system that calculates the dose of intravenous insulin that is needed based on metabolic parameters, target glucose concentration, and an individual's response to insulin. Although this tool has been validated and shown to reduce both hypoglycemia and errors in critical care settings, the utility of this software has not been examined in obstetrics. The purpose of this study was to determine whether the use of intravenous insulin dosing software in women with pregestational or gestational diabetes mellitus that requires intrapartum insulin infusion can improve the rate of glucose concentration in target range (70-100 mg/dL; 3.9-5.5 mmol/L) at the time delivery. We performed a retrospective cohort study comparing laboring patients with diabetes mellitus that required insulin infusion who were dosed by standard insulin dosing chart vs the GlucoStabilizer software program from January 2012 to December 2017. The GlucoStabilizer software program, which was implemented in May 2016, replaced the standard intravenous insulin dosing chart. Inclusion criteria were women with pregestational or gestational diabetes mellitus who were treated with an intravenous insulin infusion intrapartum for at least 2 hours. Maternal characteristics, glucose values in labor, and neonatal outcomes were extracted from delivery and neonatal records. The primary outcome was the percentage of women who achieved the target glucose range (defined as a blood glucose between 70-100 mg/dL; 3.9-5.5 mmol/L) before delivery. Parametric and nonparametric statistics were used to compare both groups; a probability value of <.05 was considered statistically significant. We identified 22 patients who were dosed by a standard insulin dosing chart and 11 patients who were dosed by the GlucoStabilizer software program during intrapartum management. The GlucoStabilizer software program was superior in achieving glucose values in target range at delivery (81.8% vs 9.1%; P<.001) compared with standard insulin dosing without increasing maternal hypoglycemia (0% vs 4.3%; P=.99). Patients whose insulin dosing was managed by the GlucoStabilizer software program also had lower mean capillary blood glucose values compared with the standard insulin infusion (102.9±5.9 mg/dL [5.7±0.33 mmol/L] vs 121.7±5.9 mg/dL [6.8±0.33 mmol/L]; P=.02). Before the initiation of the infusion, both groups demonstrated mean capillary blood glucose values outside of target range (122.6±8.8 mg/dL [6.7±0.49 mmol/L] for the GlucoStabilizer software program vs 131.9±10.1 mg/dL [7.3±0.56 mmol/L] for standard insulin treatment group; P=not significant). There were no significant differences in baseline maternal characteristics between the groups or neonatal outcomes. This study is the first to demonstrate that the use of software-guided intravenous insulin dosing in obstetrics can improve intrapartum glycemic management without increasing hypoglycemia in women with both pregestational and gestational diabetes mellitus that is treated with an insulin infusion.

Clinical and Serological Characteristics of Cold Autoimmune Hemolytic Anemia with Concomitant Cold Agglutinin and Donath-Landsteiner Antibodies

BackgroundThe two major types of cold autoimmune hemolytic anemias are cold agglutinin disease (CAD) and paroxysmal cold hemoglobinuria (PCH). In CAD, the cold agglutinin is usually IgM with anti-I specificity. In PCH, the Donath-Landsteiner (DL) antibody is a cold reacting IgG with anti-P specificity. In this study, we describe the clinical and serological characteristics of patients with autoimmune hemolytic anemia positive for both cold agglutinin and DL antibodies.MethodsOn review of our immunohematology reference laboratory database, we identified patients over a 16-year period (January 2000- March 2016) with the following: i) age ≥18 years, ii) hemoglobin (Hb) <12g/dL, iii) positive direct antiglobulin test (DAT) with hemolysis (increased lactate dehydrogenase/low serum haptoglobin/ elevated indirect bilirubin), and iv) tested for both CAD and DL antibodies. We classified the patients into 3 cohorts. Cohort 1 included patients positive for both cold agglutinin (titer ≥1:64) and DL antibodies. Cohort 2 consisted of patients with DL antibody but no cold agglutinin (titer <1:64), while Cohort 3 was comprised of patients with cold agglutinin but no DL antibody. We evaluated the clinical response based on the GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) criteria (Barcellini W, et al . Blood 2014) defined as i) complete (CR): hemoglobin ≥12 g/dL with normalization of at least one previously abnormal hemolytic marker; ii) partial (PR): hemoglobin 10-12 g/dL with hemolysis; or iii) none (NR): if any of the above criteria were not met.ResultsSeven patients had cold autoimmune hemolytic anemia with concomitant cold agglutinin and DL antibodies (Cohort 1). The clinical and serological characteristics are described in table 1. The median age at diagnosis was 68 years (range: 59-78) and the median hemoglobin at onset was 10.3 g/dL (range: 8.2-10.6). Six had red cell agglutination in the blood smear. Two patients had a recent history of infection (1 with Mycoplasma pneumoniae and 1 with upper respiratory tract infection). The median follow-up was 4.8 months (range: 1.0-166.4). Five patients received steroid/other immunosuppressants and two were managed conservatively. The clinical response to treatment was CR in 28.6% patients, PR in 42.9%, and NR in 14.3%. In comparison, Cohort 2 had a 20% CR, 20% PR and 40% NR, while Cohort 3 had a 50% CR, 25% PR and 25% NR, respectively.ConclusionOur study is the first series describing patients with cold autoimmune hemolytic anemia with concomitant cold agglutinin and DL antibodies. In terms of clinical response, patients with negative DL antibodies and cold agglutinin titers >1:64 had better response (50% CR, Cohort 3) to immunosuppressants compared to patients with positive DL antibody (20-30% CR, Cohorts 1 and 2). Large scale studies may be warranted to determine the treatment strategies among patients with concomitant DL and high cold agglutinin titers. [Display omitted] DisclosuresKay:Agios: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding; Tolero Corporation: Research Funding; Gilead: Research Funding. Winters:Fresenius Kabi USA: Consultancy; Eliaz Therapeutics Inc: Membership on an entity's Board of Directors or advisory committees; Sanofi Inc: Other: Moderated opinion leader's forum; Wiley Blackwell: Employment; Regional Health Inc: Consultancy; Mayo Clinic: Employment; Grifols International SA: Consultancy.

Smartphone-Enabled Health Coaching Intervention (iMOVE) to Promote Long-Term Maintenance of Physical Activity in Breast Cancer Survivors: Protocol for a Feasibility Pilot Randomized Controlled Trial.

BackgroundAlthough physical activity has been shown to contribute to long-term disease control and health in breast cancer survivors, a majority of breast cancer survivors do not meet physical activity guidelines. Past research has focused on promoting physical activity components for short-term breast cancer survivor benefits, but insufficient attention has been devoted to long-term outcomes and sustained exercise adherence. We are assessing a health coach intervention (iMOVE) that uses mobile technology to increase and sustain physical activity maintenance in initially inactive breast cancer survivors.ObjectiveThis pilot randomized controlled trial (RCT) is an initial step in evaluating the iMOVE intervention and will inform development of a full-scale pragmatic RCT.MethodsWe will enroll 107 physically inactive breast cancer survivors and randomly assign them to intervention or control groups at the University Health Network, a tertiary cancer care center in Toronto, Canada. Participants will be women (age 18 to 74 years) stratified by age (55 years and older/younger than 55 years) and adjuvant hormone therapy (AHT) exposure (AHT vs no AHT) following breast cancer treatment with no metastases or recurrence who report less than 60 minutes of preplanned physical activity per week. Both intervention and control groups receive the 12-week physical activity program with weekly group sessions and an individualized, progressive, home-based exercise program. The intervention group will additionally receive (1) 10 telephone-based health coaching sessions, (2) smartphone with data plan, if needed, (3) supportive health tracking software (Connected Wellness, NexJ Health Inc), and (4) a wearable step-counting device linked to a smartphone program.ResultsWe will be assessing recruitment rates; acceptability reflected in selective, semistructured interviews; and enrollment, retention, and adherence quantitative intervention markers as pilot outcome measures. The primary clinical outcome will be directly measured peak oxygen consumption. Secondary clinical outcomes include health-related quality of life and anthropometric measures. All outcome measures are administered at baseline, after exercise program (month 3), and 6 months after program (month 9).ConclusionsThis pilot RCT will inform full-scale RCT planning. We will assess pilot procedures and interventions and collect preliminary effect estimates.Trial RegistrationClinicalTrials.gov NCT02620735; https://clinicaltrials.gov/ct2/show/NCT02620735 (Archived by WebCite at https://clinicaltrials.gov/ct2/show/NCT02620735)

The effect of endotracheal tubes versus laryngeal mask airways on perioperative respiratory adverse events in infants: a randomised controlled trial

Perioperative respiratory adverse events (PRAE) are the most common critical incidents in paediatric anaesthesia and occur more often in infants. Use of laryngeal mask airways (LMAs) is associated with reduced PRAE compared with endotracheal tubes in older children (>1 year). We aimed to evaluate the effect of these devices on the incidence of PRAE in infants. We did a randomised controlled trial at the Princess Margaret Hospital for Children in Perth (WA, Australia) by recruiting infants (aged 0-12 months) undergoing general (with or without regional or local) anaesthesia with anticipated fentanyl dose 1 μg/kg or lower for minor elective surgery. We excluded patients contraindicated for LMA or endotracheal tube; who had known cardiac disease or airway or thoracic malformations; who were receiving midazolam premedication; who were undergoing airway, thoracic, or abdomen surgery at the time of participation; and if the parents did not speak English. Written parental or guardian consent was obtained before enrolment. Participants were randomly assigned (1:1), by computer-generated variable block randomisation, to receive an LMA (PRO-Breathe, Well Lead Medical Co Ltd, Panyu, China) or an endotracheal tube (Microcuff, Halyard Health Inc, Atlanta, GA, USA). Sealed randomisation envelopes were used to conceal device assignment. An interim analysis was planned once half the number of infants needed (145) had been recruited. The primary outcome was incidence of PRAE, assessed in the intention-to-treat population. The institutional ethics committee at the Princess Margaret Hospital for Children granted ethical approval (1786/EP). The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000250033). The trial began on July 8, 2010, and was ended early on May 7, 2015, after the interim analysis results met the study stopping rules. During this time, 239 infants were assessed and 181 eligible infants were randomly assigned to receive an LMA (n=85) or an endotracheal tube (n=95). Four infants were not included in the analysis (two due to cancelled procedures, one did not meet inclusion criteria, and one with missing dataset). In the intention-to-treat analysis, PRAE occurred in 50 (53%) infants in the endotracheal tube group and in 15 (18%) infants in the LMA group (risk ratio [RR] 2·94, 95% CI 1·79-4·83, p<0·0001). Laryngospasm and bronchospasm (major PRAE) were recorded in 18 (19%) infants in the endotracheal tube group and in three (4%) infants in the LMA group (RR 5·30, 95% CI 1·62-17·35, p=0·002). No deaths were reported. In infants undergoing minor elective procedures, LMAs were associated with clinically significantly fewer PRAE and lower occurrence of major PRAE (laryngospasm and bronchospasm) than endotracheal tubes. This difference should be a consideration in airway device selection. Princess Margaret Hospital Foundation, National Health and Australian Medical Research Council, Stan Perron Charitable Trust, and Callahan Estate.

External Cervical Resorption: A Comparison of the Diagnostic Efficacy Using 2 Different Cone-beam Computed Tomographic Units and Periapical Radiographs

IntroductionThe aim of this study was to compare the diagnostic efficacy of 2 cone-beam computed tomographic (CBCT) units with parallax periapical (PA) radiographs for the detection and classification of simulated external cervical resorption (ECR) lesions. MethodsSimulated ECR lesions were created on 13 mandibular teeth from 3 human dry mandibles. PA and CBCT scans were taken using 2 different units, Kodak CS9300 (Carestream Health Inc, Rochester, NY) and Morita 3D Accuitomo 80 (J Morita, Kyoto, Japan), before and after the creation of the ECR lesions. The lesions were then classified according to Heithersay's classification and their position on the root surface. Sensitivity, specificity, positive predictive values, negative predictive values, and receiver operator characteristic curves as well as the reproducibility of each technique were determined for diagnostic accuracy. ResultsThe area under the receiver operating characteristic value for diagnostic accuracy for PA radiography and Kodak and Morita CBCT scanners was 0.872, 0.99, and 0.994, respectively. The sensitivity and specificity for both CBCT scanners were significantly better than PA radiography (P < .001). There was no statistical difference between the sensitivity and specificity of the 2 scanners. The percentage of correct diagnoses according to the tooth type was 87.4% for the Kodak scanner, 88.3% for the Morita scanner, and 48.5% for PA radiography.The ECR lesions were correctly identified according to the tooth surface in 87.8% Kodak, 89.1% Morita and 49.4% PA cases. The ECR lesions were correctly classified according to Heithersay classification in 70.5% of Kodak, 69.2% of Morita, and 39.7% of PA cases. ConclusionsThis study revealed that both CBCT scanners tested were equally accurate in diagnosing ECR and significantly better than PA radiography. CBCT scans were more likely to correctly categorize ECR according to the Heithersay classification compared with parallax PA radiographs.

Implementation and Operational Research: Cost and Efficiency of a Hybrid Mobile Multidisease Testing Approach With High HIV Testing Coverage in East Africa

In 2013-2014, we achieved 89% adult HIV testing coverage using a hybrid testing approach in 32 communities in Uganda and Kenya (SEARCH: NCT01864603). To inform scalability, we sought to determine: (1) overall cost and efficiency of this approach; and (2) costs associated with point-of-care (POC) CD4 testing, multidisease services, and community mobilization. We applied microcosting methods to estimate costs of population-wide HIV testing in 12 SEARCH trial communities. Main intervention components of the hybrid approach are census, multidisease community health campaigns (CHC), and home-based testing for CHC nonattendees. POC CD4 tests were provided for all HIV-infected participants. Data were extracted from expenditure records, activity registers, staff interviews, and time and motion logs. The mean cost per adult tested for HIV was $20.5 (range: $17.1-$32.1) (2014 US$), including a POC CD4 test at $16 per HIV+ person identified. Cost per adult tested for HIV was $13.8 at CHC vs. $31.7 by home-based testing. The cost per HIV+ adult identified was $231 ($87-$1245), with variability due mainly to HIV prevalence among persons tested (ie, HIV positivity rate). The marginal costs of multidisease testing at CHCs were $1.16/person for hypertension and diabetes, and $0.90 for malaria. Community mobilization constituted 15.3% of total costs. The hybrid testing approach achieved very high HIV testing coverage, with POC CD4, at costs similar to previously reported mobile, home-based, or venue-based HIV testing approaches in sub-Saharan Africa. By leveraging HIV infrastructure, multidisease services were offered at low marginal costs.

Effects of positioning upon the vertical dimension on cone beam computed tomography

Aims: The present study was performed to investigate the effects of different positioning modalities on vertical dimensional measurements of potential implant sites in cone beam computed tomography (CBCT) images. Methods: Twenty-eight implant shaped stainless steel pins were placed in every tooth location in a dry skull and CBCT images of these pins were obtained with the skull in different positions in lateral and forward-backward planes. The following angles were used in both planes: –10°, –5°, 0°, +5° and +10°. The CBCT images were obtained with the Kodak 9000 CBCT imaging system (Carestream Health Inc, Rochester NY, USA). Panoramic slice views were used for measurement allowing all pins to be viewed on the same slice. The measurements of vertical dimensions of the pins were performed twice on the obtained images by the same observer according to tooth regions and the data was statistically analyzed. Results: Statistical analysis revealed that for forward-backward movements measurement differences were statistically significant in maxillary anterior, mandibular anterior and mandibular premolar regions and for lateral position changes statistically significant differences were observed in the maxillary premolar and maxillary molar regions for imaging modalities changing between the angles of –10° and +10°. Conclusion: Changing the skull position reduces the accuracy of vertical dimensions on CBCT scans. The results of the present study showed that skull movements between –10o and +10o effects the anterior regions significantly, but for other regions of the jaws the measurements are within a clinically acceptable range.